Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with multiple sclerosis (MS). Exercise training is a promising approach for managing cognitive dysfunction in MS; however, results from previous randomized controlled trials (RCTs) have been equivocal. This is inconsistent with the well- established literature from the general population that consistently documents beneficial effects of exercise training on cognition and brain function. Indeed, the MS RCTs suffer from significant methodological flaws and are not on par with the rigor of exercise training studies on cognition in the general population. To that end, we recently completed a line of research that identified progressive (i.e., both intensity and duration) treadmill walking exercise as an optimal exercise training intervention for improving cognitive processing speed (CPS; the most commonly impaired cognitive domain in MS) and thalamocortical resting-state functional connectivity (RSFC), in particular, among fully-ambulatory persons with MS. To that end, the purpose of the present proposal is to conduct an adequately-powered, single-blind, RCT, using an active control condition for improving CPS and brain function in cognitively-impaired persons with MS at a single research site. This study will examine the effects of 3-months of supervised, progressive chronic treadmill walking exercise (designed based on pilot work) compared with a placebo control condition (i.e., stretching- and-toning activities) on CPS, fMRI (i.e., thalamocortical RSFC), and functional outcomes in 88 persons with MS who present with slowed CPS. We will collect data on CPS, thalamocortical RSFC, and functional outcomes at baseline and follow-up (i.e., at the conclusion of the 3-month intervention period) time points. We hypothesize that treadmill walking exercise training will result in significant improvements in CPS, thalamocortical RSFC, and functional outcomes. We further speculate that improvements in thalamocortical RSFC might explain exercise-related improvements in CPS. If successful, the proposed study will provide the first Class I evidence for the effects of treadmill walking exercise training as a rehabilitative approach to improve CPS, its neural correlate, and functional consequences in persons with MS who need such an intervention the most. This line of research will lay the groundwork for the development of exercise training guidelines that can be adapted by clinicians for use by MS patients for specifically improving cognition and brain health. Such an evidence-based approach for rehabilitation, using exercise training, is paramount considering the prevalent, disabling, and poorly-managed nature of MS-related CPS impairment. This is consistent with the National Center for Medical Rehabilitation Research?s mission to foster development of scientific knowledge needed to enhance the health, productivity, independence, and quality of life of persons with physical disabilities.